Aminolevulinic Acid Hydrochloride Gel

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Transient Amnestic Episodes [see WARNINGS AND PRECAUTIONS].
• Risk of BF-RhodoLED Lamp Induced Eye Injury [see WARNINGS AND PRECAUTIONS].
• Increased Photosensitivity [see WARNINGS AND PRECAUTIONS].
• Risk of Bleeding in Patients with Coagulation Disorders [see WARNINGS AND PRECAUTIONS].
• Ophthalmic Adverse Reactions [see WARNINGS AND PRECAUTIONS].
• Risk of Mucous Membrane Irritation [see WARNINGS AND PRECAUTIONS].

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The clinical program for AMELUZ included three double-blind and placebo-controlled trials (Trials 1, 2, and 3), enrolling a total of 299 subjects that were treated with narrow band light. Trial subjects were adults greater than or equal to 49 years of age, and the majority had Fitzpatrick skin type I, II, or III. No subjects had Fitzpatrick skin type V or VI. Approximately 86% of subjects were male, and all subjects were Caucasian.

For all trials, the enrolled subjects had mild to moderate AKs (Olsen grade 1 and 2) with 4 to 8 lesions on the face and scalp. Overall, 87 placebo-treated subjects (n=16, n=32, n=39) and 212 AMELUZ-treated subjects (n=32, n=55, and n=125) were illuminated with BF-RhodoLED or similar narrow spectrum lamps.

Local skin reactions at the application site were observed in about 99.5% of subjects treated with AMELUZ and narrow spectrum lamps. The most frequent adverse reactions during and after PDT were application site erythema, pain, burning, irritation, edema, pruritus, exfoliation, scab, induration, and vesicles.

Most adverse reactions occurred during illumination or shortly afterwards, were generally of mild or moderate intensity, and lasted for 1 to 4 days in most cases; in some cases, however, they persisted for 1 to 2 weeks or even longer. Severe pain/burning occurred in up to 30% of subjects. In one case, the adverse reactions required interruption or discontinuation of the illumination.

The incidence of common (≥ 1%, <10%) and very common (≥ 10%) adverse reactions in randomized, multicenter trials at the application site are presented in Table 1.

Table 1: Incidence of Adverse Reactions Occurring at ≥ 1% of the AMELUZ Group and More Frequently than the Vehicle Group in the Actinic Keratosis Trials at the Application Site

Common (≥ 1%, <10%) adverse reactions not at the application site for AMELUZ were headache, skin exfoliation, chills and eyelid edema.

Less common (≥ 0.1%, <1%) adverse reactions at the application site for AMELUZ were hemorrhage and swelling. The adverse reactions not at the application site were blister, feeling hot, pruritus, pyrexia, scab, nervousness, pain, petechiae, rash pustular, skin erosion and ulcer.

In a clinical trial designed to investigate the sensitization potential of aminolevulinic acid with 216 healthy subjects, 13 subjects (6%) developed allergic contact dermatitis after continuous exposure for 21 days with doses of aminolevulinic acid that were higher than doses normally used in the treatment of AK.

Postmarketing Experience

The following adverse reactions have been reported during post-approval use of AMELUZ. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Skin and subcutaneous tissue disorders: application site inflammation, application site discoloration.

Eye disorders: eye irritation, diplopia, ocular hyperemia, photophobia, and blurred vision.

General disorders and administration site conditions: fatigue.

Nervous system disorders: dysaesthesia, transient amnestic episodes.

Transient Amnestic Episodes

Transient amnestic episodes have been reported with use of AMELUZ in combination with photodynamic therapy. Advise patients and their families or caregivers to contact their healthcare provider if memory impairment, confusion, or disorientation is observed [see WARNINGS AND PRECAUTIONS].

Photosensitivity

Advise patients that for approximately 48 hours following treatment to avoid exposure to sunlight, and prolonged or intense light on the treated lesion sites and surrounding skin.

Advise patients to avoid certain medications that may enhance the phototoxic reaction to PDT [see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS].

Common Adverse Reactions

Inform patients that treatment with AMELUZ in combination with PDT may result in adverse reactions which include local skin reactions at the application site such as erythema, pain/burning, irritation, edema, pruritus, exfoliation, induration, scab, and vesicles.